Successful treatment of Epstein–Barr virus–associated primary central nervous system lymphoma due to post-transplantation lymphoproliferative disorder, with ibrutinib and third-party Epstein–Barr virus–specific T cells

Law, Soi Cheng; Hoàng, Thị Thu Hương; O'Rourke, Kacey M; Tobin, Joshua W.D.; Gunawardana, Jay; Loo-Oey, Dorothy; Bednarska, Karolina; Long, Lilia Merida de; Sabdia, Muhammed B.; Hapgood, Greg; Blyth, Emily; Clancy, Leighton; Hennig, Stefanie; Keane, Colm; Gandhi, Maher K.

doi:10.1111/ajt.16628

Cited by 15 publications

(16 citation statements)

References 24 publications

(49 reference statements)

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“…Ibrutinib (Imbruvica ® ) was measured in CSF in primary CNS lymphomas [ 85 , 86 ]. In one study, hemodialysis was conducted every other day.…”

Section: Resultsmentioning

confidence: 99%

“…Six-hour post-dose CSF ibrutinib levels were about tenfold higher on hemodialysis-free days than those observed on hemodialysis days. In addition, the CSF-UPR’s (with an assumed protein-bound fraction comprising 97.3% of circulating ibrutinib) were 78% and 8%, respectively [ 85 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the majority of cases, sample pretreatment consisted of deproteinization. The removal of proteins was performed using organic solvents (acetonitrile—ceritinib [ 74 ], erlotinib [ 47 ], gefitinib [ 45 ], ibrutinib [ 85 , 86 ], imatinib [ 16 , 20 , 21 , 22 ], ponatinib [ 37 ], regorafenib [ 89 ], ribociclib [ 78 , 79 ], vemurafenib [ 68 ], venetoclax [ 95 ], zanubrutinib [ 86 ]; acetonitrile-methanol 1:1—dasatinib [ 27 ], imatinib [ 14 ], nilotinib [ 32 , 33 , 34 , 36 ]; acetonitrile-methanol 1:4—erlotinib [ 54 ]; acetonitrile-methanol 10:1—zanubrutinib [ 87 ]; methanol—alectinib [ 76 ], dabrafenib [ 69 ], dasatinib [ 12 ], erlotinib [ 46 ], nintedanib [ 12 ], panobinosat [ 12 ], regorafenib [ 12 ], ribociclib [ 12 ], trametinib [ 69 ], vorinostat [ 12 ]), and, in a single case, the aqueous dilution of perchloric acid (imatinib [ 18 ]). The deproteinization methodology was not described by Xing et al for the monitoring of osimertinib in CSF [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

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Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

et al. 2023

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Orally administered, small-molecule anticancer drugs with tumor-specific cellular protein targets (OACD) have revolutionized oncological pharmacotherapy. Nevertheless, the differences in exposure to these drugs in the systemic circulation and extravascular fluid compartments have led to several cases of therapeutic failure, in addition to posing unknown risks of toxicity. The therapeutic drug monitoring (TDM) of OACDs in therapeutically relevant peripheral fluid compartments is therefore essential. In this work, the available knowledge regarding exposure to OACD concentrations in these fluid spaces is summarized. A review of the literature was conducted by searching Embase, PubMed, and Web of Science for clinical research articles and case reports published between 10 May 2001 and 31 August 2022. Results show that, to date, penetration into cerebrospinal fluid has been studied especially intensively, in addition to breast milk, leukocytes, peripheral blood mononuclear cells, peritoneal fluid, pleural fluid, saliva and semen. The typical clinical indications of peripheral fluid TDM of OACDs were (1) primary malignancy, (2) secondary malignancy, (3) mental disorder, and (4) the assessment of toxicity. Liquid chromatography–tandem mass spectrometry was most commonly applied for analysis. The TDM of OACDs in therapeutically relevant peripheral fluid spaces is often indispensable for efficient and safe treatments.

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“…Ibrutinib (Imbruvica ® ) was measured in CSF in primary CNS lymphomas [ 85 , 86 ]. In one study, hemodialysis was conducted every other day.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

et al. 2023

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“…Many viral infections, if not cleared during the acute stages, may become chronic. Chronic infections are often associated with intermittent recrudescence, autoimmune complications and/or malignancies (1)(2)(3)(4)(5). Both the innate and acquired immune systems are involved.…”

Section: Introductionmentioning

confidence: 99%

“…These patients may benefit from virus-specific ACT used either prophylactically or therapeutically (2). Additionally, both preclinical models and clinical trials using ACT have supported its utility to treat virally driven malignancies associated with human papillomavirus (HPV) and EBV (2)(3)(4). EBV targeted ACT might further elucidate links between EBV infection and multiple sclerosis (5).…”

Section: Introductionmentioning

confidence: 99%

AIM™ platform: A new immunotherapy approach for viral diseases

et al. 2022

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In addition to complications of acute diseases, chronic viral infections are linked to both malignancies and autoimmune disorders. Lack of adequate treatment options for Epstein-Barr virus (EBV), Human T-lymphotropic virus type 1 (HTLV-1), and human papillomavirus (HPV) remains. The NexImmune Artificial Immune Modulation (AIM) nanoparticle platform can be used to direct T cell responses by mimicking the dendritic cell function. In one application, AIM nanoparticles are used ex vivo to enrich and expand (E+E) rare populations of multi-antigen-specific CD8+ T cells for use of these cells as an AIM adoptive cell therapy. This study has demonstrated using E+E CD8+ T cells, the functional relevance of targeting EBV, HTLV-1, and HPV. Expanded T cells consist primarily of effector memory, central memory, and self-renewing stem-like memory T cells directed at selected viral antigen peptides presented by the AIM nanoparticle. T cells expanded against either EBV- or HPV-antigens were highly polyfunctional and displayed substantial in vitro cytotoxic activity against cell lines expressing the respective antigens. Our initial work was in the context of exploring T cells expanded from healthy donors and restricted to human leukocyte antigen (HLA)-A*02:01 serotype. AIM Adoptive Cell Therapies (ACT) are also being developed for other HLA class I serotypes. AIM adoptive cell therapies of autologous or allogeneic T cells specific to antigens associated with acute myeloid leukemia and multiple myeloma are currently in the clinic. The utility and flexibility of the AIM nanoparticle platform will be expanded as we advance the second application, an AIM injectable off-the-shelf nanoparticle, which targets multiple antigen-specific T cell populations to either activate, tolerize, or destroy these targeted CD8+ T cells directly in vivo, leaving non-target cells alone. The AIM injectable platform offers the potential to develop new multi-antigen specific therapies for treating infectious diseases, cancer, and autoimmune diseases.

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Ibrutinib/methotrexate/rituximab

2021

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Successful treatment of Epstein–Barr virus–associated primary central nervous system lymphoma due to post-transplantation lymphoproliferative disorder, with ibrutinib and third-party Epstein–Barr virus–specific T cells

Abstract: Successful treatment of Epstein-Barr virus-associated primary central nervous system lymphoma due to post-transplantation lymphoproliferative disorder, with ibrutinib and third-party Epstein-Barr virus-specific T cells.

Cited by 15 publications

References 24 publications

Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

AIM™ platform: A new immunotherapy approach for viral diseases

Ibrutinib/methotrexate/rituximab

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